Open Access
Research
Tanis R Fenton,1,2 Tian Huang2,3
To cite: Fenton TR, Huang T.
Systematic review of the
association between dietary
acid load, alkaline water and
cancer. BMJ Open 2016;6:
e010438. doi:10.1136/
bmjopen-2015-010438
▸ Prepublication history and
additional material is
available. To view please visit
the journal (http://dx.doi.org/
10.1136/bmjopen-2015010438).
Received 4 November 2015
Revised 18 March 2016
Accepted 21 March 2016
ABSTRACT
Objectives: To evaluate the evidence for a causal
relationship between dietary acid/alkaline and alkaline
water for the aetiology and treatment of cancer.
Design: A systematic review was conducted on
published and grey literature separately for randomised
intervention and observational studies with either
varying acid–base dietary intakes and/or alkaline water
with any cancer outcome or for cancer treatment.
Outcome measures: Incidence of cancer and
outcomes of cancer treatment.
Results: 8278 citations were identified, and 252
abstracts were reviewed; 1 study met the inclusion
criteria and was included in this systematic review. No
randomised trials were located. No studies were located
that examined dietary acid or alkaline or alkaline water
for cancer treatment. The included study was a cohort
study with a low risk of bias. This study revealed no
association between the diet acid load with bladder
cancer (OR=1.15: 95% CI 0.86 to 1.55, p=0.36). No
association was found even among long-term smokers
(OR=1.72: 95% CI 0.96 to 3.10, p=0.08).
Conclusions: Despite the promotion of the alkaline diet
and alkaline water by the media and salespeople, there is
almost no actual research to either support or disprove
these ideas. This systematic review of the literature
revealed a lack of evidence for or against diet acid load
and/or alkaline water for the initiation or treatment of
cancer. Promotion of alkaline diet and alkaline water to
the public for cancer prevention or treatment is not
justified.
1
Department of Community
Health Sciences, O’Brien
Institute for Public Health,
Alberta Children’s Hospital
Research Institute, University
of Calgary, Calgary, Alberta,
Canada
2
Nutrition Services, Alberta
Health Services, Calgary,
Alberta, Canada
3
Faculty of Agriculture, Life
and Environmental Sciences,
Edmonton Clinic Health
Academy, University of
Alberta, Edmonton, Alberta,
Canada
Correspondence to
Dr Tanis R Fenton;
TFenton@ucalgary.ca
INTRODUCTION
The general public is being encouraged by
the lay press that to prevent cancer; they are
persuaded to assess the acidity of their urine
and/or saliva as an assessment of the acidity
of their body and then to modify their diets
accordingly.1–7 The alkaline diet, or acid–ash
diet, is being promoted based on the claims
that modern diets acidify the body1–11
causing diseases including cancer, osteoporosis and cardiovascular disease.1–12 The alkaline diet is also promoted for conditions
including diabetes and hypertension.
Promoters of this diet claim that changing
Strengths and limitations of this study
▪ Broad search of both the published and unpublished literature on both alkaline diets and alkaline water was conducted for studies to include
in this systematic review.
▪ We located only one observational study that fit
the inclusion criteria.
▪ The objective, to determine if evidence of a
causal relationship exists between dietary acid or
alkaline and the etiology of cancer and/or the
treatment of this disease, was defined a priori.
▪ Explicit reproducible methodology.
▪ Assessed the included study’s validity, ie risk of
bias, using a quality checklist.
food choices to more ‘alkaline’ selections
prevents all of these conditions1–9 11 and has
the ability to treat cancer once it has been
developed.5 10 12 13 This diet is based on the
concept that mineral components of foods
make the body acidic, alkaline or neutral.14
The alkaline diet is designed to provide
more alkaline ions after metabolism, based
on the acid–ash hypothesis developed over
100 years ago.15 The acid–ash hypothesis suggests that to achieve a more alkaline load,
one must consume more fruit and vegetables
with only a moderate intake of protein.
While marketing of this diet implies that the
diet changes will raise systemic pH, a wellconducted randomised trial of these diet
changes altered only systemic pH by 0.014
units, while the urine pH increased by
1.02 units.16 This study reveals that diet
changes can alter urine pH but does not
change blood pH.16 Furthermore, the fact
that the effect of phosphorus on calcium
metabolism is opposite to that was predicted
by the hypothesis17 raises questions about
the validity of the hypothesis. Additionally, a
review of the body of evidence regarding the
acid–ash/alkaline hypothesis for bone health
found that the hypothesis is not supported
and there is no evidence that altering the
diet acid load improves bone health.18
Fenton TR, Huang T. BMJ Open 2016;6:e010438. doi:10.1136/bmjopen-2015-010438
1
BMJ Open: first published as 10.1136/bmjopen-2015-010438 on 13 June 2016. Downloaded from http://bmjopen.bmj.com/ on June 18, 2022 by guest. Protected by copyright.
Systematic review of the association
between dietary acid load, alkaline
water and cancer
Open Access
METHODS
Eligibility criteria
Randomised interventions and observational human
studies of acid–base intakes of diet, supplemental salts to
change systemic pH (such as potassium bicarbonate or
potassium citrate) and consumption of alkaline water,
with cancer outcomes (both aetiology and treatment),
were sought. No language or publication date restrictions were imposed. Human participants of all ages and
backgrounds were considered. Studies with no original
research (narrative reviews, editorials) and non-human
studies were excluded from this review.
Literature search
Two reviewers conducted independent literature
searches, one with the assistance of a librarian ( J.P.), in an
attempt to find all human studies of the ash–acid diet
hypothesis or an alkaline diet with any type of cancer as
the outcome. Studies were identified through search text
words and Medical subject headings: diet, dietary, acid,
acidic, alkaline, acid-base, acid-base equilibrium, acid-ash,
2
net acid excretion (NAE), ‘potential renal acid load,
water, cancer, neoplasm’ (see online supplementary file).
For published literature, databases searched included
Ovid MEDLINE, PubMed, Cochrane Register of Clinical
Trials, CINAHL and Embase up to April 2015. No limits
were applied to searches, and studies reported in all languages were considered. In an effort to include all available studies, reference lists for the located articles were
also reviewed. For grey literature, Current Controlled
Trials, Canadian Cancer Trials, Google, and Google
Scholar were manually searched up to April 2015.
Both reviewers examined the article titles for relevance to the topic and potential fit to the inclusion criteria independently, with the plan to use discussion and
resolution by reaching consensus of any differences in
assessments. When the title was not clear regarding the
potential fit, both reviewers reviewed the abstracts. For
abstracts which suggested relevance, the full text of the
article was reviewed. Both researchers extracted data
independently. There was no indication of unpublished
data from the search, so authors were not contacted.
Data extracted included exposures to estimates of acid
generated from diet, among humans, and with the
outcome of any cancer.
Results with p values <0.05 were considered to be statistically significant, and relative risk >2.0 with no plausible residual confounding were considered clinically
relevant.26 We used the Newcastle-Ottawa Scale to assess
the included study for risk of bias.27
RESULTS
Description of studies
A total of 8278 citations were identified, and 252
abstracts were reviewed for potential fit; only 1 study met
the inclusion criteria28 and was included in this systematic review. There were no disagreements about articles’
fit to the inclusion criteria between the reviewers. The
literature search also located a systematic review that
found no evidence for the alkaline diet29 and two narrative reviews discussing the acid–ash/alkaline diet and
cancer.30 31 No relevant unpublished studies were found.
The systematic review, published in 2014, reported
finding four articles on the alkaline diet and cancer in a
Google search but it did not report findings from these
articles or their references.29
The two narrative reviews did not include any human
studies of an association between diet acid/alkaline and
cancer. The narrative review by Robey31 concluded:
“there are numerous systemic pathways affected by
diet-induced acidosis that may be cancer promoting, but
a causal role is poorly defined”. The review by Lee and
Shen30 suggested a post hoc analogy between the traditional Chinese medicine concepts of yin and yang with
the acid/alkaline diet but did not cite any studies of the
acid/alkaline diet and cancer.
The included study, by Wright et al,28 was a prospective
cohort study, nested within the α-Tocopherol,
Fenton TR, Huang T. BMJ Open 2016;6:e010438. doi:10.1136/bmjopen-2015-010438
BMJ Open: first published as 10.1136/bmjopen-2015-010438 on 13 June 2016. Downloaded from http://bmjopen.bmj.com/ on June 18, 2022 by guest. Protected by copyright.
The marketing of the alkaline diet promotes not only
a diet, but also the sale of related supplements and
water alkaliniser machines through almost every media
medium, including websites, books and videos.1–6 8 In
our experience, patients with cancer are approached by
salespeople who are promoting water alkalinisers as a
way to treat their cancer. Studies suggest that a substantial and growing number of patients use the internet to
obtain health information,19 20 which may not be
innocuous. Oncologists report that internet use by
patients with cancer contributes to confusion and
anxiety among patients with cancer.20
There is some evidence that some cancer cells and
tumours grow well in an acidic environment in the
laboratory.21 22 While the alkaline diet is being promoted
to correct the acid state that the modern diet creates, the
American Institute of Cancer Research and the Canadian
Cancer Society have stated that the body tightly regulates
systemic pH and food choices will only affect urine pH
and not body acidity.23 24 Studies show that while urine
pH changes in response to diet changes, blood pH does
not.16 25 As acid/base forming potential of foods does
alter urinary pH,16 25 cancers of the urinary tract may be
an important focus in investigating claims of the alkaline
diet to prevent and treat cancer.
As far as we are aware, no systematic review has been
done to evaluate the evidence for an association
between dietary acid and/or alkaline, or the effectiveness of alkaline water, for the aetiology or treatment of
cancer. The purpose of this systematic review is to
conduct an extensive search of the published and
unpublished literature to determine whether evidence
of a causal relationship exists between dietary acid or
alkaline and the aetiology of cancer and/or the treatment of this disease.
Open Access
Study
Population
Outcome
Results
Wright
et al28
29 133 male
residents of
southwestern
Finland, aged 50–
69 years who
smoked 5 or more
years
Relative
risk of
bladder
cancer
The relative risk
(RR) for bladder
cancer was 1.15
(CI 0.86 to 1.55,
p=0.38),
suggesting that
urine pH is not a
major risk factor
for bladder
cancer
Study
design
Potential modifiers
or confounders
Prospective
cohort study
Energy intake, age,
number of cigarettes
smoked daily, number
of years of smoking,
α-tocopherol and
β-carotene
supplementation, BMI,
total fluid intake,
education level, place
of residence,
pack-years of smoking,
smoking inhalation,
smoking cessation,
calcium, magnesium
and/or potassium
supplements
Effect modification by
smoking duration,
smoking dose, total
fluid intake, BMI and
intervention group was
evaluated in stratified
analysis
Other risk of bias
Used renal NAE
based on a validated
formula based on
nutrient intake and
anthropometric
information to
estimate true urine
pH
BMI, body mass index; NAE, net acid excretion; RR, relative risk.
β-Carotene Cancer Prevention Study, a randomised controlled trial (table 1). This study examined the diet acid
load and the occurrence of bladder cancer. The exposure used in this study was an estimate of renal NAE,
based on dietary intakes and anthropometrics. No
studies were found that examined any other cancer or
neoplastic outcomes with dietary acid, alkalinity, alkaline
water, the use of an alkaline diet, alkaline water or
change of the diet acid load for cancer treatment.
Wright et al28 examined the relationship between
diet-estimated renal NAE using a food frequency questionnaire (and measured height and weight for the estimation of urinary organic acid excretion) with the risk
of bladder cancer in a large cohort of 27 096 male
smokers.28 The relative risk estimate for bladder cancer
was 1.15 (CI 0.86 to 1.55, p=0.38) for individuals in the
most acidic versus the least acidic NAE quintile as
assessed in a multivariate proportional hazards model, a
not statistically significant relationship. These researchers also tested whether acidic urine was associated with
an increased risk of bladder cancer in a subset of longterm smokers. Among men who smoked for more than
45 years, there was a non-significant, adjusted relative
risk of bladder cancer of 1.72 (CI 0.96 to 3.10, p=0.08)
with higher NAE levels.
Risks of bias assessment
Overall, we rated the Wright study28 as having a low risk
of bias since it warranted a score of 7 out of a possible 9
on the Newcastle-Ottawa Scale.27 We reduced the score
from a full 9/9 since food frequency questionnaires are
imperfect descriptions of exposure to nutrients,32 and
due to possible residual confounding. Additionally, since
the study by Wright et al28 was a prospective observational
study, this study had the strength of temporality, since the
exposure (estimated urine acidity) preceded the outcome
(bladder cancer risk). The study relied on estimated
renal NAE to determine urine acidity, which could potentially result in misclassification of individuals.
DISCUSSION
This systematic review, based on only one relevant observational study, did not find support for the acid–ash
hypothesis which suggests that acid from the diet causes
or contributes to cancer development.1–6 The GRADE
working group recommends that any associations from
observational data are weak evidence unless the results
show at least a twofold risk with no concerns about confounding, or a fivefold risk with narrow CIs when there
are remaining concerns about bias.26 The estimates of
effect between the diet acid load and bladder cancer in
this study were not statistically significant, and the estimates of effect were low relative to the GRADE
guidelines.
The included Wright study28 had strengths of having a
low risk of bias on the Newcastle-Ottawa Scale27 and temporality between the exposure (NAE) and bladder
cancer risk and controlled for several potentially
Fenton TR, Huang T. BMJ Open 2016;6:e010438. doi:10.1136/bmjopen-2015-010438
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Table 1 Included study
Open Access
4
of ciprofloxacin on human bladder cell lines suggests
that the antiproliferative potential and antitumour effect
of this drug may be superior at low urine pH.40 Overall,
safety considerations for increasing urinary pH in
patients with bladder cancer undergoing certain cancer
therapy treatments needs to be evaluated before the
patients should undertake urine pH alterations.
Future study direction may focus on systematic reviews
to examine the relationships between the alkaline diet
and other health conditions. Several observational prospective studies have suggested a relationship between
acid load and risk of type 2 diabetes41 42 as well as hypertension.43 44 However, in all three of these studies, the
estimates of effect are of low magnitude, below the
threshold of the relative risk of 2, the minimum considered to indicate important associations.26 Furthermore,
these studies had large sample sizes (1732–66 485);
small significant p values are likely in studies with large
sample sizes even when there is no important effect.45
Other prospective studies have suggested a lack of association between the dietary acid load and risks of type 2
diabetes46 as well as hypertenstion.47 Furthermore, in
observational studies, residual confounding is likely;26
many lifestyle variables are interrelated. Therefore, it is
not recommended to suggest that the findings from
such studies represent independent causal relationships.48 It must be noted that although observational
studies are important in generating hypotheses, intervention studies are required to investigate and confirm
associations between diet and disease.
The alkaline diet emphasises, to varying degrees, fresh
fruits, vegetables, roots and tubers, and legumes with
only a moderate protein intake. It is possible that some of
these foods may have cancer-protective effects, not
through their acidity/alkaline-promoting qualities but
rather due to nutrient and non-nutritive compounds.
A systematic review and meta-analysis of prospective
studies show that a high intake of dietary fibre is associated with reduced risk of colorectal cancer.49 A review
and meta-analysis of epidemiological research on physical
activity, diet and adiposity found that a prudent dietary
pattern of high intakes of fruits, vegetables, whole grains,
legumes and fish appeared to be protective against breast
cancer.50 However, the alkaline diet promotes the exclusion of many foods, and several of which contribute many
beneficial nutrients and have health benefits.
CONCLUSIONS
Despite the promotion of the alkaline diet and alkaline
water by the media and salespeople, there is almost no
actual research to either support or disprove them. A systematic review of the literature revealed a lack of evidence of an association between a diet acid load or
alkaline water for cancer risk and no studies alkaline
treatment for cancer. Promotion of alkaline diet and
alkaline water to the public for cancer prevention or
treatment is not justified.
Fenton TR, Huang T. BMJ Open 2016;6:e010438. doi:10.1136/bmjopen-2015-010438
BMJ Open: first published as 10.1136/bmjopen-2015-010438 on 13 June 2016. Downloaded from http://bmjopen.bmj.com/ on June 18, 2022 by guest. Protected by copyright.
cofounding variables. These study strengths provide
support that the study reached accurate conclusions.
Our thorough literature search did not locate any
studies of this acid/alkali hypothesis for any other forms
of cancer or cancer treatment. Additionally, our literature search failed to locate any studies that evaluated
whether alkaline water has a role in prevention or treatment of cancer. Thus, there is a lack of support for any
advice to the public about the acid–ash hypothesis, the
alkaline diet and/or alkaline water and their relationships to cancer. By searching the published and unpublished literature for studies on this topic, we decreased
the risk of publication bias. It is a limitation of this study
that we located only one observational study.
Some review articles suggest that alterations in acid–
base homeostasis in the tumour microenvironment are
common in the pathology of cancer21 22 and that
tumour interstitial fluid has a reduced buffering capacity
compared with normal tissues, and along with high rates
of production of metabolic end products, tumours may
cause an acidic extracellular environment.22 Furthermore,
cancer therapy may be influenced by pH. Some in vitro
and animal studies have suggested that metabolic alkalosis
may be useful in enhancing some cancer treatment
regimens.33
However, these in vitro examinations and animal
studies of cancer cell behaviour are at the hypothesisgenerating phase and should not be extrapolated to
human health. These cell culture studies do not address
the questions or provide evidence regarding cancer aetiology or treatment. Studies have demonstrated that alkaline supplements25 or alkaline-promoting diets16 can
alter urine pH; however, they do not appreciably change
overall systemic pH.16 25 Three studies of acid load interventions have measured both urine and blood pH
changes as a result of various interventions, including
changes in food intake,16 ingesting a bicarbonate salt25
or a phosphate salt.34 In each case, the urine pH
increased markedly, from 0.2 to 1.2 pH units, while
blood pH did not changed minimally, by 0.0116 25 to
0.0234 pH units. The urine pH changes were 7.534 to
17725 multiples of the blood pH changes. This comparison shows that kidneys are effective at excreting acid to
maintain systemic pH balance and that urine pH does
not provide a measurement of systemic pH.
In spite of finding no human studies of alkaline water
and cancer, our search did locate some studies of
alkaline water; however, none of which supported the
promotions that suggest alkaline water supports good
health. We found outcomes from alkaline water
included: in humans, inhibited gastric secretion,35
reduced gall bladder emptying,36 and toxic reactions;37
in rat pups: cardiac necrosis38 and growth restriction.39
Therefore, the promotion of alkaline water as health
promoting is not supported by evidence.
There may be a safety concern involving eating an
‘alkaline diet’ and subsequently to increase urine pH of
patients with bladder cancer. For instance, the influence
Open Access
Funding This research received no specific grant from any funding agency in
the public, commercial or not-for-profit sectors.
24.
25.
26.
27.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
28.
Data sharing statement No additional data are available.
Open Access This is an Open Access article distributed in accordance with
the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build upon this work noncommercially, and license their derivative works on different terms, provided
the original work is properly cited and the use is non-commercial. See: http://
creativecommons.org/licenses/by-nc/4.0/
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Young RO. The pH miracle—balance your diet, reclaim your health.
New York: Warner Books, 2002.
Eating Veggies. 2012. http://eating-veggies.com (accessed 27 Jul
2015).
Alkaline diet for Cancer. 2012. http://www.acidalkalinediet.com/
alkaline-diet-for-cancer (accessed 27 Jul 2015).
The Alkaline Guy. 2012. http://www.youtube.com/watch?
v=2HtoDmAtgt4 (accessed 27 Jul 2015).
Cancer Alkaline Diet is the Natural Cure. 2012. http://www.youtube.
com/watch?v=ttm3q7kweL4 (accessed 27 Jul 2015).
Ohsawa G. Acid & Alkaline—an overview of pH and human health.
2012.
Corrett N. Le Regime Alcalin. Paris: Larousse, 2015.
Sebastian A, Frassetto L, Merriam R, et al. Estimation of the net acid
load of the diet of ancestral preagricultural Homo sapiens and their
hominid ancestors. Am J Clin Nutr 2002;76:1308–16.
Sebastian A, Morris RC. Improved mineral balance and skeletal
metabolism in postmenopausal women treated with potassium
bicarbonate. N Engl J Med 1994;331:279.
Marra J. Cause, cure, and cancer free: how I became a cancer free
escapee. Pennsylvania: Sakura Publishing and Technologies, 2014.
Jackson G. Alkaline foods for the alkaline diet: fell the pH miracle of the
healthy pH diet. Createspace Independent Publishing Platform, 2014.
American Anit-Cancer Institute. http://www.americanaci.org/
Alkaline pH diet. 2012. http://www.alkalinephdiet.com/
alkaline-diet-for-cancer-patients/ (accessed 27 Jul 2015).
Dwyer J, Foulkes E, Evans M, et al. Acid/alkaline ash diets: time for
assessment and change. J Am Diet Assoc 1985;85:841–5.
Sherman H, Gettler A. The balance of acid-forming and
base-forming elements in foods, and its relation to ammonia
metabolism. J Biol Chem 1912;11:323–38.
Buclin T, Cosma M, Appenzeller M, et al. Diet acids and alkalis
influence calcium retention in bone. Osteoporos Int 2001;12:493–9.
Fenton TR, Lyon AW, Eliasziw M, et al. Phosphate decreases urine
calcium and increases calcium balance: a meta-analysis of the
osteoporosis acid-ash diet hypothesis. Nutr J 2009;8:41.
Fenton TR, Tough SC, Lyon AW, et al. Causal assessment of
dietary acid load and bone disease: a systematic review &
meta-analysis applying Hill’s epidemiologic criteria for causality. Nutr
J 2011;10:41.
Pautler SE, Tan JK, Dugas GR, et al. Use of the internet for
self-education by patients with prostate cancer. Urology
2001;57:230–3.
Helft PR, Hlubocky F, Daugherty CK. American oncologists’ views of
internet use by cancer patients: a mail survey of American Society of
Clinical Oncology members. J Clin Oncol 2003;21:942–7.
McCarty MF, Whitaker J. Manipulating tumor acidification as a
cancer treatment strategy. Altern Med Rev 2010;15:264–72.
Gillies RJ, Raghunand N, Garcia-Martin ML, et al. pH imaging. A
review of pH measurement methods and applications in cancers.
IEEE Eng Med Biol Mag 2004;23:57–64.
American Institute for Cancer Research. Questions about body pH
and Cancer. 2012. http://www.aicr.org/press/health-features/
nutrition-wise/nw-questions-about-body-ph-and-cancer-mets-stevia.
html (accessed 27 Jul 2015).
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
Fenton TR, Huang T. BMJ Open 2016;6:e010438. doi:10.1136/bmjopen-2015-010438
Canadian Cancer Society. 2012. http://www.cancer.ca/en/
prevention-and-screening/be-aware/cancer-myths-and-controversies/
an-alkaline-diet-and-cancer/?region=on (accessed 27 Jul 2015).
Maurer M, Riesen W, Muser J, et al. Neutralization of Western diet
inhibits bone resorption independently of K intake and reduces
cortisol secretion in humans. Am J Physiol Renal Physiol 2003;284:
F32–40.
Guyatt GH, Oxman AD, Sultan S, et al. GRADE guidelines: 9. Rating
up the quality of evidence. J Clin Epidemiol 2011;64:1311–16.
Wells GA, Shea B, Connell DO, et al. The Newcastle-Ottawa Scale
(NOS) for assessing the quality of nonrandomised studies in metaanalyses. 2000. http://www.ohri.ca/programs/clinical_epidemiology/
oxford.asp (accessed 15 May 2016).
Wright ME, Michaud DS, Pietinen P, et al. Estimated urine pH and
bladder cancer risk in a cohort of male smokers (Finland). Cancer
Causes Control 2005;16:1117–23.
Huebner J, Marienfeld S, Abbenhardt C, et al. Counseling patients
on cancer diets: a review of the literature and recommendations for
clinical practice. Anticancer Res 2014;34:39–48.
Lee MM, Shen JM. Dietary patterns using traditional Chinese
medicine principles in epidemiological studies. Asia Pac J Clin Nutr
2008;17(Suppl 1):79–81.
Robey IF. Examining the relationship between diet-induced acidosis
and cancer. Nutr Metab (Lond) 2012;9:72.
Ioannidis JP. Implausible results in human nutrition research. BMJ
2013;347:f6698.
Raghunand N, Gillies RJ. pH and chemotherapy. Novartis Found
Symp 2001;240:199–211; discussion 265–8.
Krapf R, Glatz M, Hulter HN. Neutral phosphate administration
generates and maintains renal metabolic alkalosis and
hyperparathyroidism. Am J Physiol 1995;268:F802–7.
Drobnik M. [Evaluation of pharmacodynamic properties of
medium-mineralized alkaline water designed for distribution as
bottled natural mineral water]. Rocz Państwowego Zakładu Hig
2000;51:379–84.
Gasbarrini G, Arienti V, Magri F, et al. [Effects of bicarbonatedalkaline water (Uliveto) on gastric and gallbladder emptying in
normal subjects. Ultrasonic evaluation]. Minerva Med
1991;82:59–62.
Lendowski L, Färber H, Holy A, et al. Accidental contamination of a
German town’s drinking water with sodium hydroxide. Int J Hyg
Environ Health 2015;218:366–9.
Watanabe T, Kishikawa Y, Shirai W. Influence of alkaline ionized
water on rat erythrocyte hexokinase activity and myocardium.
J Toxicol Sci 1997;22:141–52.
Merne ME, Syrjänen KJ, Syrjänen SM. Systemic and local effects of
long-term exposure to alkaline drinking water in rats. Int J Exp Pathol
2001;82:213–19.
Gurtowska N, Kloskowski T, Drewa T. Ciprofloxacin criteria in
antimicrobial prophylaxis and bladder cancer recurrence. Med Sci
Monit 2010;16:RA218–23.
Akter S, Eguchi M, Kuwahara K, et al. High dietary acid load is
associated with insulin resistance: the Furukawa Nutrition and
Health Study. Clin Nutr 2016;35:453–9.
Fagherazzi G, Vilier A, Bonnet F, et al. Dietary acid load and risk of
type 2 diabetes: the E3N-EPIC cohort study. Diabetologia
2014;57:313–20.
Akter S, Eguchi M, Kurotani K, et al. High dietary acid load is
associated with increased prevalence of hypertension: the Furukawa
Nutrition and Health Study. Nutrition 2015;31:298–303.
Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and
risk of incident hypertension in United States women. Hypertension
2009;54:751–5.
Higgins J, Green S, eds. Cochrane handbook for systematic reviews
of interventions version 5.1.0. 2011. http://www.cochrane-handbook.
org
Engberink MF, Bakker SJL, Brink EJ, et al. Dietary acid load and
risk of hypertension: the Rotterdam study. Am J Clin Nutr
2012;95:1438–44.
Xu H, Jia T, Huang X, et al. Dietary acid load, insulin sensitivity and
risk of type 2 diabetes in community-dwelling older men.
Diabetologia 2014;57:1561–8.
Ioannidis JP, Loy EY, Poulton R, et al. Researching genetic versus
nongenetic determinants of disease: a comparison and proposed
unification. Sci Transl Med 2009;1:7ps8.
Aune D, Chan DSM, Greenwood DC, et al. Dietary fiber and breast
cancer risk: a systematic review and meta-analysis of prospective
studies. Ann Oncol 2012;23:1394–402.
Patterson RE, Cadmus LA, Emond JA, et al. Physical activity, diet,
adiposity and female breast cancer prognosis: a review of the
epidemiologic literature. Maturitas 2010;66:5–15.
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Contributors TRF conceptualised and designed the study, and TH assisted in
the conceptualisation and design of the study and drafted the initial
manuscript. Both authors conducted comprehensive literature searches,
conducted the analysis and interpretation of data for the work, reviewed and
revised the manuscript, approved the final manuscript as submitted, and
agree to be accountable for all aspects of the work.